1. Field of the Invention
The present invention relates to a substantially purified immunosuppressive polypeptide (ISP), a process of preparing the same and uses therefor.
2. Brief Description of the Background Art
Despite the many advances in the care of critically injured patients, such as modern intensive care, resuscitation, and anesthetic techniques and an increasing arsenal of powerful antibiotics, death from overwhelming sepsis and multisystem organ failure remains a problem. In these patients host-defenses have become deficient and are no longer able to recognize and eradicate invasive organisms.
The first barrier to invasion by microorganisms is the epithelium of the skin, respiratory tract, and gastrointestinal tract. If this barrier is penetrated, then both specific and non-specific means of destroying microbial invaders are brought into play. Non-specific defense mechanisms include polymorphonuclear (PMN) and mononuclear phagocytes, natural killer cells (NK), products of complement activation, and certain acute phase proteins, particularly C-reactive protein. Specific defense mechanisms include antibody formation by B-lymphocytes, direct microbial killing by T lymphocytes, and T lymphocyte activation of mononuclear phagocytes. Many abnormalities of both the specific and non-specific host-defensive mechanisms have been described in critically injured patients, including burn patients.
Increased circulating suppressor cell activity has been described in burn and trauma patients and in appropriate animal models. McIrvine, Ann. Surg., 196: 297 (1982); Munster, Lancet, 1: 1329 (1976); Miller, et al., J. Clin. Invest., 63: 202 (1979); Wang, et al., J. Clin. Invest., 66: 200 (1980); Ninnemann, et al., J. Clin. Invest., 3: 142 (1983); Wang, et al., Clin. Immunol. Immunopathol., 24: 161 (1982). The transfer of decreased resistance to infection to normal mice by splenic cells from syngeneic burned mice has been reported. Kupper, et al., J. Surg. Res., 38: 606 (1985). Suppression of lymphocyte activation by serum or serum fractions from seriously injured patients has also been repeatedly reported. Constantian, et al., Ann. Surg., 185: 73 (1977); Ninnemann, in The Immune Consequence of Thermal Injury (J. L. Ninnemann, ed.), Williams and Wilkins, Baltimore and London, 1981, pp. 66-89; Ozkan, et al., J. Clin. Immunol., 5: 172 (1985); Kato, et al., J. Immunol, 133: 2025 (1984). That serum factors play a role in the immune deficiency seen in trauma and burn patients was first suggested by the present Applicants. Constantian, et al., Ann. Surg., 185: 73 (1977). One of these serum factors, immunosuppressive polypeptide (ISP) is the subject of the present invention. The serum suppressive activity is found chiefly in low molecular weight polypetide-containing fractions.